Long-term epidemiologic studies on large numbers of night and rotating shift workers have suggested an increase in the incidence of breast and colon cancer in these populations. These studies suffer from poor definition and quantification of the work schedules of the exposed subjects. Against this background, the pathophysiology of phase shift and phase adaptation is reviewed. A phase shift as experienced in night and rotating shift work involves desynchronization at the molecular level in the circadian oscillators in the central nervous tissue and in most peripheral tissues of the body. There is a change in the coordination between oscillators with transient loss of control by the master-oscillator (the Suprachiasmatic Nucleus, SCN) in the hypothalamus. The implications of the pathophysiology of phase shift are discussed for long-term health effects and for the design of ergonomic work schedules minimizing the adverse health effects upon the worker.

The relationship between circadian phototransduction and circadian-regulated processes is poorly understood. Melatonin, commonly a circadian phase marker, may play a direct role in a myriad of physiologic processes. The circadian rhythm for pineal melatonin secretion is regulated by the hypothalamic suprachiasmatic nucleus (SCN). Its neural source of light input is a unique subset of intrinsically photosensitive retinal ganglion cells expressing melanopsin, the primary circadian photopigment in rodents and primates. Action spectra of melatonin suppression by light have shown that light in the 446-477 nm range, distinct from the visual system's peak sensitivity, is optimal for stimulating the human circadian system. Breast cancer is the oncological disease entity whose relationship to circadian rhythm fluctuations has perhaps been most extensively studied. Empirical data has increasingly supported the hypothesis that higher risk of breast cancer in industrialized countries is partly due to increased exposure to light at night. Studies of tumor biology implicate melatonin as a potential mediator of this effect. Yet, causality between lifestyle factors and circadian tumor biology remains elusive and likely reflects significant variability with physiologic context. Continued rigorous empirical inquiry into the physiology and clinical implications of these habitual, integrated aspects of life is highly warranted at this time.